1. Field of the Invention
The present invention relates to a novel gene coding human epidermal growth factor and a process for preparing the same. Specifically, the present invention relates to a novel human epidermal growth factor gene and a process for preparing the same employing a recombinant expression vector therefor.
2. Description of the Prior Art
It is known that human epidermal growth factor (hereinafter referred to as `hEGF`) is a polypeptide hormone consisting of 53 amino acids and 3 disulfide bridges[see: Cohen, S., J. Biol. Chem., 237:1555-1562(1962); Savage, C. R., Jr. et al., J. Biol. Chem., 248:7669-7672(1973); Savage, C. R., Jr. et al., J. Biol. Chem., 247:7612-7621 (1972)], and that hEGF plays an important role on the growth control in mammalian cells, inter alia epidermal and epithelial cells on molecular level[see: Sporn, M. B. et al., Nature (London), 313:745-747(1985); Sporn, M. B. et al., N. Engl. J. Med., 303:878-880(1980)] and the treatment of injury [see: Buckley, A. et al., Proc. Natl. Acad. Sci., USA, 82: 7340-7344(1985)]. Further, it has been reported that the hEGF can be applied in the treatment of a stomach ulcer, due to its ability to repress secretion of gastric acid into stomach[see: Gregory, H., J. Cell Sci. Suppl., 3: 11-17(1985)].
Under the circumstances, studies on the mass production of the hEGF has been actively carried out, since Starkey et al. reported the biochemical property of hEGF purified from human urine[see: Starkey, R. H. et al., Science, 189:800(1975); Cohen, S. et al., Proc. Natl. Acad. Sci., USA, 72:1317(1975)]. Several researchers have accomplished cloning of hEGF gene by the recombinant DNA technology in a successful manner[see: Smith, J. et al., Nucleic Acids Res., 10:4467-4482(1982); Urdea, M. S . et al., Proc. Natl. Acad. Sci., USA, 80:7461-7465(1983); Oka, T. et al., Proc. Natl. Acad. Sci., USA, 82:7212-7216(1985)]. The prior art, however, has not described methods of producing hEGF to the level sufficient for industrial application, due to its low activity and productivity.
Accordingly, studies on the elevation of activity and productivity in hEGF manufacture have been carried out. These studies have concentrated on the preparation of the nucleotide sequence of hEGF gene efficient for its massive production and the expression vector whose regulatory function is strengthened.